Npc2, also known as HE1, is a gene encoding a 132-amino-acid glycoprotein. It is a crucial transporter for cholesterol trafficking, working in coordination with NPC1 and directly interacting with the membrane of late endosome and lysosome [1,3]. Cholesterol trafficking is an essential process that impacts various cellular functions, and Npc2's role in this pathway is of great biological significance. Genetic models, such as mouse models, are valuable for studying Npc2's function.

In Npc2-deficient mouse models (Npc2Gt(LST105)BygNya), six-week-old pre-symptomatic mice showed splenomegaly and neuropathological changes, especially in the cerebellum with initial Purkinje cell loss and neuroinflammation. By 12 weeks, the mice had growth retardation, tremor, cerebellar ataxia, splenomegaly, foam cell accumulation in multiple organs, brain atrophy, pronounced Purkinje cell degeneration, and severe neuroinflammation, resembling the pathology of human Niemann-Pick type C2 disease [2]. In zebrafish, npc2-deficient mutants exhibited low mobility, high anxiety-related response, downregulation of genes related to mitochondrial function and myelination, and pathological changes in multiple organs associated with inflammatory responses, suggesting it as a model for NPC disease [4].

In conclusion, Npc2 is vital for cholesterol trafficking. The study of Npc2 through gene-knockout models, like in mice and zebrafish, has revealed its significant role in Niemann-Pick type C2 disease and related pathological conditions, providing insights into the complex mechanisms underlying the disease and potential targets for treatment.